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Biomedical subjects

S Huber

Publications and source records attributed to S Huber.

At least 37 records · Page 2Linked to original sources

Estrus and estrogen changes in mated and unmated free-living European ground squirrels.

The course of behavioral and vaginal estrus and patterns of circulating estrogens were followed in free-living European ground squirrels (Spermophilus citellus) after their emergence from hibernation. Normally mating females were compared to a second group in an area where males had been removed from the population before female emergence. Both groups showed vaginal estrus, but the patterns differed. Mating shortened vaginal estrus to a 3-day period compared to 8 days in unmated females. The extent (cell number) of cell cornification during estrus and the cellular components (percentage distribution) of metestrus did not differ between the two groups. Females in the area without males had significantly higher estrogen levels during estrus and metestrus compared to those in the control area. European ground squirrels were found to be monestrous, as none of the unmated females reentered estrus after metor diestrus was detected. The prolongation of vaginal estrus in unmated females can be viewed as either a physiological inevitability or an adaptation to low mate availability. The extension is still relatively short compared to other sciurid species and perhaps a product of constraints producing a strict time frame for reproduction.

Animals↗

Successful treatment of massive arterial air embolism during open heart surgery.

We report a case of a 5-year-old girl who suffered a massive arterial air embolism during surgical closure of an atrial septal defect. The risk of permanent neurologic deficits or even fatal outcome is significant (mortality rate, 31%). We successfully treated a proven arterial air embolism with intraoperative (retrograde cerebral perfusion) combined with postoperative procedures (deep barbiturate anesthesia and hyperbaric oxygenation). At discharge the girl had fully recovered from the initial neurologic defects.

Child, Preschool↗

Contrast-enhanced power Doppler harmonic imaging--influence on visualization of renal vasculature.

To compare contrast-enhanced power Doppler (PD) harmonic imaging (CHI) with contrast-enhanced power Doppler fundamental imaging (CPD) in the depiction of renal cortical vessels, 20 healthy volunteers were subjected to PD imaging and HI assessment of the kidney after bolus injection of Levovist(R) (SH U 508A). System settings were standardized and the pulse-repetition frequencies (PRF) systematically toggled from 750 to 500 and 250. Videotapes were independently reviewed by three readers with regard to the presence of artefacts, the degree of Doppler signal enhancement, demarcation of vessels and the extent of visualization. The assessments were graded separately for each PRF in accordance with a multistage scoring system. In comparison to contrast-enhanced PD, artefacts were significantly lower with CHI for all PRF (p = 0.0001). Vessels were better visualized (p = 0.002) and less blurred (p = 0.006) with CHI than with CPD. There was no significant difference in the extent of Doppler signal increase between CPD and the contrast-enhanced harmonic mode. Combination of the contrast-enhanced harmonic method and PD allows the PRF to be lowered and, by balancing the greater susceptibility of PD to interference from clutter, increases the likelihood of detection of flow in small vessels.

Adult↗

Relevance of sonographic B-mode criteria and computer-aided ultrasonic tissue characterization in differential/diagnosis of solid breast masses.

We aimed to evaluate the differential diagnostic value of a method of computer-assisted texture analysis in comparison to established ultrasonographic B-mode characteristics in the examination of solid breast masses. At two centers, 77 patients presenting with a solid mass on B-mode scan were studied at 7.5 MHz. Description of B-mode appearance included assessment of tumor shape, borders, presence of an echogenic rim, tissue architecture, internal echo structure, absorption and elasticity. For statistical pattern recognition, the following parameters were used: form factor, mean grey level, signal-to-noise ratio, mean gradient and correlation from the co-occurrence matrix. At center 1, the most decisive parameter for differential diagnosis was distortion of tissue architecture (sensitivity, SN, 83%; specificity, SP, 92%) and, at center 2, relation to the adjacent tissue (SN 93%, SP 92%). Among texture parameters, best discrimination was achieved for correlation from the co-occurrence matrix at center 1 (SN 58%, SP 73%) and for form factor at center 2 (SN 93%, SP 77%). Among sonographic criteria, the highest contribution to the diagnosis was found for an unsharp border (odds ratio, OR, 12.2), architectural distortion (OR, 8.6), fixation to skin or chest wall (OR, 9.0) and fixation to adjacent breast parenchyma (OR, 8.8), according to texture analysis for parameters form factor (OR 4.0) and correlation from the co-occurrence matrix (OR 4.7). Ultrasonographic texture analysis can be helpful as an additional parameter in differential diagnosis of breast tumors, but did not reach differential diagnostic accuracy of sonomorphologic features.

Adult↗

Analytical evaluation of primer engineered multiplex polymerase chain reaction-restriction fragment length polymorphism for detection of factor V Leiden and prothrombin G20210A.

Factor V Leiden and prothrombin G20210A are clinically relevant genetic risk factors for venous thrombosis. Analysis for both mutations is increasingly being performed on patients exhibiting hypercoagulability. The goal of the current study was to evaluate the performance of primer-engineered multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the simultaneous detection of factor V Leiden and prothrombin G20210A. Primer-engineered multiplex PCR-RFLP methods for the detection of factor V Leiden and prothrombin G20210A from the medical literature were reviewed. A modified method was optimized in which both mutations generate HindIII RFLPs and the prothrombin amplicon contains an invariant HindIII recognition site to assess the completeness of endonuclease digestion. Digested amplification products were analyzed by agarose gel electrophoresis in a single gel lane and visualized by ethidium bromide. Primer-engineered multiplex PCR-RFLP was used to analyze 205 human genomic DNA samples whose factor V Leiden genotypes had been previously determined by MnlI PCR-RFLP. Complete concordance for factor V Leiden genotypes was observed between the two methods in the 205-sample cohort comprising 139 wild-type, 62 heterozygous mutant, and four homozygous mutant individuals. For prothrombin G20210A, primer-engineered multiplex PCR-RFLP identified 196 wild-type and nine heterozygous mutant individuals in the 205-sample cohort. To independently verify prothrombin genotypes, the nine heterozygous mutants and an additional 11 wild-type patient samples (representing 10% of patient samples) were subjected to DNA sequencing. Complete concordance was observed between DNA sequencing and primer-engineered multiplex PCR-RFLP results. In further validation, 123 of the DNA samples consisting of four heterozygous mutant and 119 wild type individuals were genotyped with the Invader Assay for Factor II (prothrombin G20210A). Results showed 100% concordance between the Invader Assay and primer-engineered multiplex PCR-RFLP. A primer-engineered multiplex PCR-RFLP based on single restriction endonuclease digestion has been evaluated and shown to simultaneously and accurately detect factor V Leiden and prothrombin G20210A mutations. The method is robust and readily adaptable to the clinical molecular diagnostic laboratory.

Amino Acid Substitution↗

Characterization of lineage-specific chimaerism in patients with acute leukaemia and myelodysplastic syndrome after allogeneic stem cell transplantation before and after relapse.

Recently, we have shown that patients with acute leukaemias and myelodysplastic syndromes (MDS), who showed increasing mixed chimaerism (MC) upon serial PCR analysis after transplant, have a significantly increased risk of relapse. To determine whether the increasing MC in these patients is caused by the reappearance of normal recipient haematopoiesis or by the reoccurrence of malignant cells, we purified different leucocyte subpopulations and analysed these subfractions with regard to their donor-recipient ratio by a PCR-based method for the analysis of minisatellite DNA regions. In 14 patients [eight acute lymphoblastic leukaemia (ALL), three acute myelogenous leukaemia (AML) and three MDS] subfractions were analysed when increasing MC was first noted upon serial analysis of the peripheral blood. In seven of these 14 patients (four ALL, two AML and one MDS), subfractions were characterized at the time of frank haematological relapse. In all 14 patients investigated with increasing MC, recipient cells were detected in different mononuclear cell subpopulations. In patients characterized during frank relapse, two distinct distribution patterns were found. Patients who relapsed before day +300 (one ALL, two AML and one MDS) showed recipient-derived (normal) cells in addition to blast populations in different mononuclear subsets as well as granulocytes. In patients with acute leukaemias who relapsed after day +300 (two ALL and one AML), only leukaemic cells were found that were of recipient origin, whereas all other haematopoietic cell lines were donor derived. These data show that persistent MC in the early post-transplant period is caused predominantly by normal recipient haematopoietic cells. This finding further supports the hypothesis that a state of mixed haematopoietic chimaerism may reduce the clinical graft-versus-leukaemia (GVL) effect of alloreactive donor-derived effector cells in patients with acute leukaemias and MDS, and thus facilitate the proliferation of residual malignant cells that may have survived the preparative regimen.

Adolescent↗

A protein with similarity to the human retinoblastoma binding protein 2 acts specifically as a repressor for genes regulated by the b mating type locus in Ustilago maydis.

Pathogenic development in the corn smut fungus Ustilago maydis is controlled by a heterodimer of the two homeodomain proteins bE and bW which are encoded by the b mating type locus. The bE/bW heterodimer is thought to achieve its function as a transcriptional regulator of pathogenicity genes, either directly by binding to cis regulatory sequences or indirectly via a b-dependent regulatory cascade. In a screen for components of the b-dependent regulatory cascade we have isolated Rum1 (regulator U. maydis 1), a protein with similarities to the human retinoblastoma binding protein 2. Deletion of rum1 results in expression of several b regulated genes independently from their activation via the bE/bW heterodimer. rum1 mutant strains remain pathogenic, proliferate in planta, but fail to produce spores. The defect leads to an arrest in spore development at a defined stage before the spore wall is generated. Deduced from the highly conserved domain structure of Rum1 that includes a DNA-binding motif and a region known to facilitate the interaction with histone deacetylases, we propose that Rum1 functions as a transcriptional repressor through the modulation of chromatin structure.

Amino Acid Sequence↗

[Vascularization of fibroadenomas: contrast harmonic imaging compared with contrast-enhanced power doppler].

PURPOSE: To compare contrast material-enhanced harmonic power Doppler ultrasonography (CHI) with conventional contrast-enhanced power Doppler ultrasound (CPD) in depicting the vascularity of fibroadenomas. MATERIALS AND METHODS: Forty patients with fibroadenomas (aged 19-61 years) underwent conventional contrast-enhanced and harmonic power Doppler US. According to a standardized examination protocol, serial dynamic scans were obtained before and at 30, 90 and 150 seconds after injection of contrast agent. Video-taped scans were independently reviewed by three blinded readers with regard to parameter artifacts, degree of Doppler signal enhancement, demarcation of vessels and extent of vessel visualization. RESULTS: The number of intratumoral power Doppler signals depicted was similar with both techniques at 30-90 seconds after contrast administration; however, after 90 seconds, CPD depicted significantly more intratumoral signals than did CHI (p < 0.0001). CHI was superior to CPD with regard to "blooming" or motion-related artifacts (p < 0.0001). CONCLUSION: CHI balances the increased susceptibility of CPD to interference from clutter artifacts and thus allows the depiction of vessels that may have been obscured on CPD at similar system settings.

Adult↗

Cell volume in the regulation of cell proliferation and apoptotic cell death.

Cell proliferation must - at some time point - lead to increase of cell volume and one of the hallmarks of apoptosis is cell shrinkage. At constant extracellular osmolarity those alterations of cell volume must reflect respective changes of cellular osmolarity which are hardly possible without the participation of cell volume regulatory mechanisms. Indeed, as shown for ras oncogene expressing 3T3 fibroblasts, cell proliferation is paralleled by activation of Na(+)/H(+) exchange and Na(+),K(+),2Cl(-) cotransport, the major transport systems accomplishing regulatory cell volume increase. Conversely, as evident from CD95-induced apoptotic cell death, apoptosis is paralleled by inhibition of Na(+)/H(+) exchanger and by activation of Cl(-) channels and release of the organic osmolyte taurine, major components of regulatory cell volume decrease. However, ras oncogene activation leads to activation and CD95 receptor triggering to inhibition of K(+) channels. The effects counteract the respective cell volume changes. Presumably, they serve to regulate cell membrane potential, which is decisive for Ca(++) entry through I(CRAC) and the generation of cytosolic Ca(++) oscillations in proliferating cells. As a matter of fact I(CRAC) is activated in ras oncogene expressing cells and inhibited in CD95-triggered cells. Activation of K(+) channels and Na(+)/H(+) exchanger as well as Ca(++) oscillations have been observed in a wide variety of cells upon exposure to diverse mitogenic factors. Conversely, diverse apoptotic factors have been shown to activate Cl(-) channels and organic osmolyte release. Inhibition of K(+) channels is apparently, however, not a constant phenomenon paralleling apoptosis which in some cells may even require the operation of K(+) channels. Moreover, cell proliferation may at some point require activation of Cl(-) channels. In any case, the alterations of cell volume are obviously important for the outcome, as cell shrinkage impedes cell proliferation and apoptosis can be elicited by increase of extracellular osmolarity. At this stage little is known about the interplay of cell volume regulatory mechanisms and the cellular machinery leading to mitosis or death of the cell. Thus, considerable further experimental effort is required in this exciting area of cell physiology.

Apoptosis↗

Ultrasonographic tissue characterization in monitoring tumor response to neoadjuvant chemotherapy in locally advanced breast cancer (work in progress).

A program of computer-assisted texture analysis was applied to evaluate its usefulness for objective description of changes in tumor architecture due to primary medical treatment in patients with locally advanced breast cancer. Changes in values of parameters of the statistical pattern recognition technique were compared to ultrasonographically depictable, subjectively recorded changes in echogenicity and echotexture (brightness, homogeneity) and reviewed with regard to histopathologic evaluation of tumor regression. Characteristic trends of defined quantitative texture parameters (mean gradient, mean gray value, contrast from the co-occurrence matrix) corresponded to visually depictable changes of the B-mode image and underlying histopathologic changes. The results indicate that quantitative texture analysis may aid in noninvasive monitoring of tumor response to neoadjuvant chemotherapy.

Adult↗

Locally advanced breast carcinoma: computer assisted semiquantitative analysis of color Doppler ultrasonography in the evaluation of tumor response to neoadjuvant chemotherapy (work in progress).

We aimed to evaluate objectively the value of color Doppler flow imaging in the assessment of response of locally advanced breast cancer to primary medical treatment by using a computer assisted semiquantitative method. Prior to and after neoadjuvant treatment, 17 patients with locally advanced breast carcinoma were prospectively evaluated by physical examination and computer assisted semiquantitative color Doppler ultrasonography. The results of clinical and color Doppler examination were finally correlated to the histopathologic evaluation of tumor response. The degree of concordance between posttherapeutic histopathologic results, clinical examination, and color Doppler assessment was evaluated by kappa statistics. Concordance was 0.474 (0.135-0.813) between histopathologic results and clinical posttherapeutic assessment and 0.870 (0.627-1.113) between histopathologic results and semiquantitative color Doppler examination. Objective semiquantitative assessment of tumor vascularity as displayed by color Doppler ultrasonography has potential as a functional tool for measuring tumor response to neoadjuvant chemotherapy.

Adult↗

Matrix metalloproteinase upregulation in chronic inflammatory demyelinating polyneuropathy and nonsystemic vasculitic neuropathy.

OBJECTIVE: To determine the expression pattern and cellular source of matrix metalloproteinases (MMPs) in chronic inflammatory demyelinating polyneuropathy (CIDP) and nonsystemic vasculitic neuropathy (NSVN). BACKGROUND: MMPs are endopeptidases involved in tissue destruction and infiltration by immune cells in multiple sclerosis and Guillain-Barré syndrome. Enzyme inhibitors of MMPs attenuate clinical symptoms in corresponding animal models of these diseases. MMP inhibition may therefore be a novel approach for the treatment of CIDP and NSVN. However, the spectrum of MMPs expressed in chronic inflammatory neuropathies has not been established. METHODS: The expression of MMP-2, MMP-3, MMP-7, and MMP-9 in T cells, macrophages, and stromal cells in CIDP, NSVN, and noninflammatory neuropathies (NIN) was quantitated by immunohistochemistry. Results were correlated with clinical and electrophysiologic findings. RESULTS: The production of MMP-2 and MMP-9 is increased in nerve tissue in CIDP and NSVN compared with NIN. T cells are the predominant source of MMP-2 and MMP-9 in CIDP and NSVN, whereas macrophages contribute only to a minor extent. Stromal cells of the perineurium/epineurium are an additional source of MMP-2 in NSVN, but not in CIDP. Expression of MMP-3 and MMP-7 was not detectable in CIDP or NSVN. Expression of MMP-2 and MMP-9 did not correlate with clinical disease activity and electrophysiologic measurements. CONCLUSIONS: The upregulation of MMP-2 and MMP-9 is a specific feature of CIDP and NSVN, and selective inhibitors of these enzymes could be used to prevent inflammatory tissue damage. The similar increase of MMP-2 and MMP-9 in both demyelinating (CIDP) and nondemyelinating (NSVN) neuropathies raises doubts about whether MMPs play a primary role in demyelination.

Adult↗

Randomized in vitro and in vivo evaluation of different biopsy needles and devices for breast biopsy.

In an experimental study (in vitro and in vivo) we evaluated the efficacy of various biopsy needles/devices for breast biopsy. In vitro, biopsies of five human cadaveric breast specimens were performed using 33 different needles/devices ranging from 14 to 20-gauge. Of these 33 needles/devices, 22 optimally performing needles were selected for the in vivo study. In the clinical part of the study, 44 breast lesions were randomly biopsied with each of the 22 needles/devices under stereotactic guidance. Tissue specimens were analysed quantitatively and qualitatively. Several automatic long-throw guns (Acecut, Asap, Biopty, Magnum) obtained greater tissue areas and had a better histopathologic score than the conventional type of a side-notch needle like Trucut, an aspiration needle like Surecut, or an end-cut needle like Autovac. The automatic long-throw guns performed better than the short-throw Monopty gun. Regardless of needle size (14-20-gauge), breast biopsies should be routinely performed with automated long-throw side-notch guns (Acecut, Asap, Biopty, Magnum).

Adult↗

Assessment of SNRPN expression as a molecular tool in the diagnosis of Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is associated with lesions of the paternal chromosome 15q11- 13. Recently, loss of expression of a paternally expressed gene in this region, SNRPN, has been proposed as a molecular hallmark of PWS. The goal of this study was to determine the diagnostic accuracy of SNRPN expression in a well-characterized cohort of PWS patients. METHODS: SNRPN expression was analyzed by reverse transcription coupled to polymerase chain reaction (RT-PCR). RNA was isolated from peripheral blood leukocytes and subjected to multiplex RT-PCR in which expression of SNRPN and a constituitively expressed internal control gene were analyzed. The amplified products were electrophoresed in agarose gels and visualized by ethidium bromide staining. RESULTS: Multiplex RT-PCR was applied to RNAs isolated from 30 normal control subjects and 30 well- characterized PWS patients. All control patients expressed the SNRPN and internal control genes. In contrast, all 30 PWS patients demonstrated loss of SNRPN expression, with integrity of RNA being demonstrated by the presence of internal control gene expression. CONCLUSIONS: Loss of SNRPN expression appears to be a consistent finding in PWS. Expression analysis of SNRPN offers a novel approach for the diagnostic evaluation of PWS that is robust and can be performed in a single day.

Adolescent↗

Adult celiac disease: US signs.

PURPOSE: To examine whether distinct ultrasonographic (US) signs exist in patients with adult celiac disease. MATERIALS AND METHODS: In a partly retrospective study, abdominal sonograms were obtained in 11 patients with adult celiac disease. Fifty matched control subjects also were examined. After the patients had fasted overnight, they were examined with 2-4-MHz abdominal and high-frequency 5-10-MHz linear-array US transducers. RESULTS: The authors found several US pathologic signs in patients with untreated disease, including abnormal fluid-filled small intestine in all 11 patients, flaccid and moderately dilated small-bowel loops (2.5-3.5 cm) in eight, slight diffuse thickening of the small-bowel wall (3-5 mm) in seven, increased peristalsis of the small intestine in eight, enlarged mesenteric lymph nodes (anteroposterior diameter 5-10 mm) in nine, dilated caliber of the superior mesenteric artery or portal vein in seven, free fluid in the abdominal cavity in five, and increased echogenicity of the liver in six. None of these signs was present in the control group. CONCLUSION: There are several US signs associated with adult celiac disease. None of the signs identified is specific, but a combination of signs is characteristic and indicates suspicion of this disease in a high percentage of cases. US could help to avoid diagnostic delay, especially in patients who have atypical clinical presentations.

Adult↗

Prostate cancer tumor grade differentiation with dynamic contrast-enhanced MR imaging in the rat: comparison of macromolecular and small-molecular contrast media--preliminary experience.

PURPOSE: To differentiate prostate cancers of different histopathologic grades with dynamic gadolinium-enhanced magnetic resonance (MR) imaging. Results with a conventional small-molecular contrast medium (CM) were compared to those with a prototypic macromolecular CM. MATERIALS AND METHODS: High- and low-grade tumors, sublines of the Dunning R3327 rat prostate cancer line, were subcutaneously implanted into the flanks of 12 male Copenhagen rats. Dynamic contrast material-enhanced MR imaging was performed with small-molecular CM and macromolecular CM at an interval of 1 day. Microvascular permeability, as estimated with the endothelial transfer coefficient, and fractional plasma volume were calculated for each tumor and each CM by means of a two-compartmental, bidirectional kinetic model. RESULTS: Mean endothelial transfer coefficient values for both macromolecular CM and small-molecular CM were significantly different between the two tumor sublines (P = .0004 and P = .01, respectively). For the high- and low-grade tumors, no overlap of values was seen with macromolecular CM, but a broad overlap was seen with small-molecular CM despite a significant difference in mean values. CONCLUSION: Dynamic contrast-enhanced MR imaging permits differentiation of histopathologic prostatic tumor types. Quantitative microvascular permeability characteristics estimated from macromolecular CM-enhanced data were significantly superior to those derived from small-molecular CM-enhanced data.

Adenocarcinoma↗